Step by Step
Init
Initiation — free radical attacks the membrane
Lipid peroxidation begins when a reactive oxygen species (ROS) such as hydroxyl radical (·OH) abstracts a hydrogen atom from an unsaturated fatty acid in the membrane, creating a lipid radical (L·). The double bonds of unsaturated fatty acids make them particularly vulnerable — more double bonds = more susceptible.
Memory trick: Initiation = the spark. One free radical steals a hydrogen and starts the fire.
Prop
Propagation — self-sustaining chain reaction
The lipid radical (L·) reacts with oxygen → lipid peroxyl radical (LOO·). LOO· steals a hydrogen from another fatty acid → lipid hydroperoxide (LOOH) + new lipid radical (L·). This new L· can propagate the chain. One initiation event can destroy thousands of membrane lipids — the chain reaction amplifies the damage massively.
Memory trick: Propagation = the fire spreads. Each burnt molecule lights the next one.
Term
Termination — chain breakers stop it
The chain reaction is terminated when: two radicals combine (quench each other), or an antioxidant donates a hydrogen to the lipid radical without itself becoming reactive. Vitamin E (α-tocopherol) is the primary fat-soluble antioxidant — it breaks the chain by donating H to LOO·. Vitamin C regenerates vitamin E.
Memory trick: Vitamin E = fire extinguisher. Donates hydrogen → quenches the radical → stops the chain.
Dmg
Consequences of lipid peroxidation
Membrane damage: loss of fluidity, increased permeability, protein dysfunction. Atherosclerosis: oxidized LDL (from lipid peroxidation) is taken up by macrophages → foam cells → plaque. MDA (malondialdehyde) and 4-HNE are reactive aldehydes formed from peroxidized lipids — they crosslink proteins and DNA. Reperfusion injury: burst of ROS after restoring blood flow.
Applied Walkthrough
1
A hydroxyl radical (·OH) from ionizing radiation attacks an unsaturated fatty acid in a cell membrane — abstracting a hydrogen and creating a lipid radical (L·).
2
L· reacts with O₂ → LOO· (lipid peroxyl radical). LOO· attacks a neighboring unsaturated fatty acid → LOOH + new L·. The chain propagates.
3
Vitamin E (in the membrane) donates a hydrogen to LOO· → stops the chain at that point. Vitamin E radical is relatively stable and quenched by vitamin C.
4
In atherosclerosis, LDL trapped in arterial walls undergoes lipid peroxidation → oxidized LDL → taken up by macrophages → foam cells → fatty streak → plaque formation.
Exam Application
Exams test the three stages of lipid peroxidation (initiation, propagation, termination), why unsaturated fatty acids are more vulnerable, vitamin E as the primary chain-breaking antioxidant, and the link between oxidized LDL and atherosclerosis. MDA as a biomarker of oxidative stress and the regeneration of vitamin E by vitamin C are also commonly tested.
⚠ Common Trap
Students think all lipids are equally susceptible to peroxidation — only UNSATURATED fatty acids are vulnerable (the double bonds are the target). Saturated fatty acids are resistant. Also: vitamin E stops the PROPAGATION stage (chain reaction) — it cannot prevent initiation. Antioxidants reduce oxidative damage; they cannot eliminate ROS entirely.
✓ Quick Self-Check
1. Why are unsaturated fatty acids more susceptible to lipid peroxidation?
Their double bonds weaken adjacent C-H bonds, making the hydrogen easier to abstract by a free radical — initiating the chain reaction.
Tap to reveal / hide
2. What is the propagation stage of lipid peroxidation?
The self-sustaining chain reaction where lipid radicals react with oxygen → peroxyl radicals → attack new fatty acids → generating new radicals. One initiation event can destroy thousands of lipid molecules.
Tap to reveal / hide
3. How does vitamin E stop lipid peroxidation?
Vitamin E donates a hydrogen atom to the lipid peroxyl radical (LOO·), quenching it and terminating the chain reaction without becoming a reactive radical itself.
Tap to reveal / hide
4. What is the connection between lipid peroxidation and atherosclerosis?
LDL in arterial walls undergoes lipid peroxidation → oxidized LDL → taken up by macrophages → foam cells → atherosclerotic plaque formation.
Tap to reveal / hide
5. How does vitamin C help vitamin E?
Vitamin C (water-soluble) regenerates vitamin E (fat-soluble) after it has donated a hydrogen — restoring it to active antioxidant form.
Tap to reveal / hide